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Articles 1 - 8 of 8
Full-Text Articles in Medicine and Health Sciences
Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta
Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta
Department of Cancer Biology Faculty Papers
Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in
Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness, Pratyusha Mandal, Lynsey Nagrani, Liliana Hernandez, Anita Louise Mccormick, Christopher Dillon, Heather Koehler, Linda Roback, Emad S Alnemri, Douglas Green, Edward Mocarski
Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness, Pratyusha Mandal, Lynsey Nagrani, Liliana Hernandez, Anita Louise Mccormick, Christopher Dillon, Heather Koehler, Linda Roback, Emad S Alnemri, Douglas Green, Edward Mocarski
Department of Biochemistry and Molecular Biology Faculty Papers
Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochon-drial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially …
Distinct Mechanisms Control Genome Recognition By P53 At Its Target Genes Linked To Different Cell Fates., Marina Farkas, Hideharu Hashimoto, Yingtao Bi, Ramana V Davuluri, Lois Resnick-Silverman, James J. Manfredi, Erik W. Debler, Steven B. Mcmahon
Distinct Mechanisms Control Genome Recognition By P53 At Its Target Genes Linked To Different Cell Fates., Marina Farkas, Hideharu Hashimoto, Yingtao Bi, Ramana V Davuluri, Lois Resnick-Silverman, James J. Manfredi, Erik W. Debler, Steven B. Mcmahon
Department of Biochemistry and Molecular Biology Faculty Papers
The tumor suppressor p53 integrates stress response pathways by selectively engaging one of several potential transcriptomes, thereby triggering cell fate decisions (e.g., cell cycle arrest, apoptosis). Foundational to this process is the binding of tetrameric p53 to 20-bp response elements (REs) in the genome (RRRCWWGYYYN0-13RRRCWWGYYY). In general, REs at cell cycle arrest targets (e.g. p21) are of higher affinity than those at apoptosis targets (e.g., BAX). However, the RE sequence code underlying selectivity remains undeciphered. Here, we identify molecular mechanisms mediating p53 binding to high- and low-affinity REs by showing that key determinants of the code are embedded …
Repurposing Niclosamide For Targeting Pancreatic Cancer By Inhibiting Hh/Gli Non-Canonical Axis Of Gsk3Β, Jyoti B. Kaushal, Rakesh Bhatia, Ranjana K. Kanchan, Pratima Raut, Surya Mallapragada, Quan P. Ly, Surinder K. Batra, Satyanarayana Rachagani
Repurposing Niclosamide For Targeting Pancreatic Cancer By Inhibiting Hh/Gli Non-Canonical Axis Of Gsk3Β, Jyoti B. Kaushal, Rakesh Bhatia, Ranjana K. Kanchan, Pratima Raut, Surya Mallapragada, Quan P. Ly, Surinder K. Batra, Satyanarayana Rachagani
Journal Articles: Biochemistry & Molecular Biology
Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive …
Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden
Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden
All ETDs from UAB
The determination of cell fate is a dynamic process regulated by hundreds of proteins that converge into complex cell signaling pathways. Upon irreparable intracellular stress, a cell undergoes programmed cell death, a process known as intrinsic apoptosis. Apoptosis is regulated by the Bcl-2 family, a class of proteins that act either as pro-survival or pro-death signaling molecules. Due to the oncogenic upregulation of pro- survival Bcl-2 family proteins across human cancer cell types, a novel class of small molecule inhibitors called ‘BH3-mimetics’ have emerged as promising anti-cancer therapeutics currently under clinical investigation. Here, we highlight the crosstalk between anti-apoptotic Bcl-2 …
The Effect Of Testosterone Replacement Therapy On Bladder Functions, Histology, Apoptosis,And Rho-Kinase Expression In Bladder Outlet Obstruction And Hypogonadism Rat Model, Bariş Saylam, Ozan Efesoy, Rabi̇a Bozdoğan Arpaci, Ruki̇ye Nalan Ti̇fti̇k, Mesut Tek, Kansu Büyükafşar, Murat Bozlu, Selahi̇tti̇n Çayan
The Effect Of Testosterone Replacement Therapy On Bladder Functions, Histology, Apoptosis,And Rho-Kinase Expression In Bladder Outlet Obstruction And Hypogonadism Rat Model, Bariş Saylam, Ozan Efesoy, Rabi̇a Bozdoğan Arpaci, Ruki̇ye Nalan Ti̇fti̇k, Mesut Tek, Kansu Büyükafşar, Murat Bozlu, Selahi̇tti̇n Çayan
Turkish Journal of Medical Sciences
Background/aim: The effect of testosterone replacement therapy was investigated on bladder functions, histology, apoptosis as well as Rho-kinase expression in the rat bladder outlet obstruction (BOO) and hypogonadism models. Materials and methods: 30 mature male rats divided into 4 groups: sham group (n = 8), BOO group (n = 8), BOO + orchiectomy group (n = 7), BOO + orchiectomy + testosterone (T) treatment group (n = 7). Cystometric findings, apoptosis index, Rho-kinase (ROCK-2) expression, and smooth muscle/collagen ratio were compared. Results: BOO did not change ROCK-2 expression level, compared to sham group (P > 0.05). However, when compared to BOO …
What Is The Restorative Effect Of Vegf Inhibitor Bevacuzimab Against Subarachnoidhemorrhage In An Experimental Model?, Adnan Yalçin Demi̇rci̇, Yahya Güvenç, Ersi̇n Özeren, Çeti̇n Akyol, Pinar Bayram, Deni̇z Bi̇llur, Sevi̇m Aydin, Hakan Seçki̇n, Kazim Yi̇ği̇tkanli
What Is The Restorative Effect Of Vegf Inhibitor Bevacuzimab Against Subarachnoidhemorrhage In An Experimental Model?, Adnan Yalçin Demi̇rci̇, Yahya Güvenç, Ersi̇n Özeren, Çeti̇n Akyol, Pinar Bayram, Deni̇z Bi̇llur, Sevi̇m Aydin, Hakan Seçki̇n, Kazim Yi̇ği̇tkanli
Turkish Journal of Medical Sciences
Background/aim: This study investigated the effect of vascular endothelial growth factor (VEGF) inhibitor bevacuzimab (BVZ) on the rabbit basilar artery using an experimental subarachnoid hemorrhage (SAH) model. Materials and methods: Eighteen adult male New-Zealand white rabbits were randomly divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH+BVZ group (n = 6). Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 10 mg/kg, intravenous BVZ for 2 days after the SAH. Basilar artery diameters were measured with …
The Protective Effects Of Anakinra In A Neonatal Rat Model Of Necrotizing Enterocolitis, Hati̇ce Güneş, Sevcan İpek, Sadik Yurttutan, Tuncay Kuloğlu, Fatma İnanç Tolun, Ülkü Kazanci, Adem Doğaner
The Protective Effects Of Anakinra In A Neonatal Rat Model Of Necrotizing Enterocolitis, Hati̇ce Güneş, Sevcan İpek, Sadik Yurttutan, Tuncay Kuloğlu, Fatma İnanç Tolun, Ülkü Kazanci, Adem Doğaner
Turkish Journal of Medical Sciences
Background/aim: Necrotizing enterocolitis (NEC) is a commonly seen life-threatening condition in newborns characterized by ischemic necrosis. This study aimed to investigate anakinra's effects, an interleukin-1 receptor antagonist, on oxidative stress, inflammation, and tissue necrosis in an NEC rat model. Materials and methods: Forty Wistar albino pups were divided into four groups randomly as follows; group 1, control group; group 2, anakinra-treated control group; group 3, NEC group; and group 4, NEC and anakinra treatment group. The rats were given hyperosmolar formula feeding, and they were exposed to hypoxia after cold stress at +4 °C and oxygen in order to create …